title: EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages.
abstract: Historically, consumption of Green tea (Camellia sinensis) has been associated with health benefits against multiple diseases including cancer, atherosclerosis and cardiovascular disorders. Emerging evidence has suggested a pathogenic role for HMGB1, a newly identified "late" mediator of lethal systemic inflammation, in the aforementioned diseases. Here we demonstrated that a major ingredient of Green tea, EGCG, was internalized into HMGB1-containing LC3-positive cytoplasmic vesicles (likely autophagosomes) in macrophages, and induced HMGB1 aggregation in a time-dependent manner. Furthermore, EGCG stimulated LC3-II production and autophagosome formation, and inhibited LPS-induced HMGB1 up-regulation and extracellular release. The EGCG-mediated HMGB1 inhibitory effects were diminished by inhibition of class III phosphatidylinositol-3 kinase (with 3-methyladenine) or knockdown of an essential autophagy-regulating protein, beclin-1. Moreover, the EGCG-mediated protection against lethal sepsis was partly impaired by co-administration of an autophagy inhibitor, chloroquine. Taken together, the present study has suggested a possibility that EGCG inhibits HMGB1 release by stimulating its autophagic degradation.
authors.affiliation: The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.forename: Andrei
authors.initials: A
authors.lastname: Assa
authors.forename: Arvin
authors.initials: A
authors.lastname: Jundoria
authors.forename: Jianying
authors.initials: J
authors.lastname: Xu
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
authors.forename: N Tony
authors.initials: NT
authors.lastname: Eissa
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sama
authors.forename: Haichao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D034622:RNA Interference; D051381:Rats
chemical_list: D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D002392:Catechin; C045651:epigallocatechin gallate